Journalartikel

Jahr der Veröffentlichung: 2008

Seiten: 6175-6186

Zeitschrift: Oncogene

Bandnummer: 27

Heftnummer: 47

ISSN: 0950-9232

eISSN: 1476-5594

DOI Link: https://doi.org/10.1038/onc.2008.220

Verlag: Springer Nature [academic journals on nature.com]

Abstract: 

The RAS association domain family 1A (RASSF1A) gene is located at chromosome 3p21.3 within a specific area of common heterozygous and homozygous deletions. RASSF1A frequently undergoes promoter methylation-associated inactivation in human cancers. Rassf1a−/− mice are prone to both spontaneous and carcinogen-induced tumorigenesis, supporting the notion that RASSF1A is a tumor suppressor. However, it is not fully understood how RASSF1A is involved in tumor suppression pathways. Here we show that overexpression of RASSF1A inhibits centrosome separation. RASSF1A interacts with Aurora-A, a mitotic kinase. Surprisingly, knockdown of RASSF1A by siRNA led to reduced activation of Aurora-A, whereas overexpression of RASSF1A resulted in increased activation of Aurora-A, suggesting that RASSF1A is involved in Aurora-A activation. Like other Aurora-A activators, RASSF1A was also a substrate of Aurora-A in vitro. The failure of recombinant RASSF1A to activate recombinant Aurora-A indicates that RASSF1A may not activate Aurora-A directly and suggests that RASSF1A may function as a scaffold to bring together Aurora-A and its activator(s). Inhibition of centrosome separation by RASSF1A overexpression is most likely a consequence of hyperstabilization of microtubules by this protein.

Harvard-Zitierstil: Liu, L., Guo, C., Dammann, R., Tommasi, S. and Pfeifer, G. (2008) RASSF1A interacts with and activates the mitotic kinase Aurora-A, Oncogene, 27(47), pp. 6175-6186. https://doi.org/10.1038/onc.2008.220

APA-Zitierstil: Liu, L., Guo, C., Dammann, R., Tommasi, S., & Pfeifer, G. (2008). RASSF1A interacts with and activates the mitotic kinase Aurora-A. Oncogene. 27(47), 6175-6186. https://doi.org/10.1038/onc.2008.220